Insights into the pulmonary vascular complications of heart failure with preserved ejection fraction

Pulmonary hypertension in the setting of heart failure with preserved ejection fraction (PH-HFpEF) is a growing public health problem that is increasing in prevalence. While PH-HFpEF is defined by a high mean pulmonary artery pressure, high left ventricular end-diastolic pressure and a normal ejection fraction, some HFpEF patients develop PH in the presence of pulmonary vascular remodelling with a high transpulmonary pressure gradient or pulmonary vascular resistance. Ageing, increased left atrial pressure and stiffness, mitral regurgitation, as well as features of metabolic syndrome, which include obesity, diabetes and hypertension, are recognized as risk factors for PH-HFpEF. Qualitative studies have documented that patients with PH-HFpEF develop more severe symptoms than those with HFpEF and are associated with more significant exercise intolerance, frequent hospitalizations, right heart failure and reduced survival. Currently, there are no effective therapies for PH-HFpEF, although a number of candidate drugs are being evaluated, including soluble guanylate cyclase stimulators, phosphodiesterase type 5 inhibitors, sodium nitrite and endothelin receptor antagonists. In this review we attempt to provide an updated overview of recent findings pertaining to the pulmonary vascular complications in HFpEF in terms of clinical definitions, epidemiology and pathophysiology. Mechanisms leading to pulmonary vascular remodelling in HFpEF, a summary of pre-clinical models of HFpEF and PH-HFpEF, and new candidate therapeutic strategies for the treatment of PH-HFpEF are summarized

Long time scale molecular dynamics using least action

We present here an efficient method for evaluating molecular trajectories over long time scales. The method is based on optimisation of the path action defined by classical mechanics. We test the technique on non-trivial examples drawn from the literature and discuss the effectiveness of this approach in the study of molecular processes. Many of the present techniques for calculating molecular trajectories are limited computationally. Standard forward integration of Newton's equations of motion yields accurate results for a range of systems whose transition times are many orders of magnitude less than most biologically interesting processes. If one wants to extend these calculations to biologically relevant time scales, it is necessary to develop methodologies which avoid this limitation. The process outlined in this paper has been tested on simple systems using harmonic and Lennard--Jones potential energy functions. The algorithm yields stable trajectories and is adjustable to suite available computational resources. In theory, this algorithm is applicable to any molecular system where the initial and final states are known. This could include investigation of chemical reactions, ligand/receptor binding and work cycles of molecular machinery

A systematic review of lumped-parameter equivalent circuit models for real-time estimation of lithium-ion battery states

This paper presents a systematic review for the most commonly used lumped-parameter equivalent circuit model structures in lithium-ion battery energy storage applications. These models include the Combined model, Rint model, two hysteresis models, Randles' model, a modified Randles' model and two resistor-capacitor (RC) network models with and without hysteresis included. Two variations of the lithium-ion cell chemistry, namely the lithium-ion iron phosphate (LiFePO4) and lithium nickel-manganese-cobalt oxide (LiNMC) are used for testing purposes. The model parameters and states are recursively estimated using a nonlinear system identification technique based on the dual Extended Kalman Filter (dual-EKF) algorithm. The dynamic performance of the model structures are verified using the results obtained from a self-designed pulsed-current test and an electric vehicle (EV) drive cycle based on the New European Drive Cycle (NEDC) profile over a range of operating temperatures. Analysis on the ten model structures are conducted with respect to state-of-charge (SOC) and state-of-power (SOP) estimation with erroneous initial conditions. Comparatively, both RC model structures provide the best dynamic performance, with an outstanding SOC estimation accuracy. For those cell chemistries with large inherent hysteresis levels (e.g. LiFePO4), the RC model with only one time constant is combined with a dynamic hysteresis model to further enhance the performance of the SOC estimator

Erythrocytes and Vascular Function: Oxygen and Nitric Oxide

Erythrocytes regulate vascular function through the modulation of oxygen delivery and the scavenging and generation of nitric oxide (NO). First, hemoglobin inside the red blood cell binds oxygen in the lungs and delivers it to tissues throughout the body in an allosterically regulated process, modulated by oxygen, carbon dioxide and proton concentrations. The vasculature responds to low oxygen tensions through vasodilation, further recruiting blood flow and oxygen carrying erythrocytes. Research has shown multiple mechanisms are at play in this classical hypoxic vasodilatory response, with a potential role of red cell derived vasodilatory molecules, such as nitrite derived nitric oxide and red blood cell ATP, considered in the last 20 years. According to these hypotheses, red blood cells release vasodilatory molecules under low oxygen pressures. Candidate molecules released by erythrocytes and responsible for hypoxic vasodilation are nitric oxide, adenosine triphosphate and S-nitrosothiols. Our research group has characterized the biochemistry and physiological effects of the electron and proton transfer reactions from hemoglobin and other ferrous heme globins with nitrite to form NO. In addition to NO generation from nitrite during deoxygenation, hemoglobin has a high affinity for NO. Scavenging of NO by hemoglobin can cause vasoconstriction, which is greatly enhanced by cell free hemoglobin outside of the red cell. Therefore, compartmentalization of hemoglobin inside red blood cells and localization of red blood cells in the blood stream are important for healthy vascular function. Conditions where erythrocyte lysis leads to cell free hemoglobin or where erythrocytes adhere to the endothelium can result in hypertension and vaso constriction. These studies support a model where hemoglobin serves as an oxido-reductase, inhibiting NO and promoting higher vessel tone when oxygenated and reducing nitrite to form NO and vasodilate when deoxygenated. How erythrocytes modulate vascular tone has been widely studied over the last two decades. The vasodilation of the vasculature under hypoxic conditions has inspired much research ranging from the effect of oxygen partial pressure on smooth muscle cell contractility and endothelial nitric oxide synthase (eNOS) activity to nitrite reduction by hemoglobin (Hb) inside erythrocytes and subsequent production of nitric oxide. Here we review how red blood cells (RBCs) and hemoglobin regulate vascular function and blood flow

Emergence of chaotic hysteresis in a second-order non-autonomous chaotic circuit

The observation of hysteresis in the dynamics of a third-order autonomous chaotic system namely, the {\it{Chua's}} circuit has been reported recently \cite{Gomes2023}. In the present work, we make a detailed study on the emergence of dynamical hysteresis in a simple second-order non-autonomous chaotic system namely, the {\it{Murali-Lakshmanan-Chua }} (MLC) circuit. The experimental realization of chaotic hysteresis is further validated by numerical simulation and analytical solutions. The presence of chaotic hysteresis in a second-order non-autonomous electronic circuit is reported for the first time. Multistable regions are observed in the dynamics of MLC with constant bias.Comment: 27 Pages, 10 figure

Battery energy storage systems for the electricity grid: UK research facilities

Grid-connected battery energy storage systems with fast acting control are a key technology for improving power network stability and increasing the penetration of renewable generation. This paper describes two battery energy storage research facilities connected to the UK electricity grid. Their performance is detailed, along with hardware results, and a number of grid support services are demonstrated, again with results presented. The facility operated by The University of Manchester is rated at 236kVA, 180kWh, and connected to the 400V campus power network, The University of Sheffield operates a 2MVA, 1MWh facility connected to an 11kV distribution network

Collinear mecanum drive: modelling, analysis, partial feedback linearisation, and nonlinear control

The Collinear Mecanum Drive (CMD) is a novel robot locomotion system, capable of generating omnidirectional motion whilst simultaneously dynamically balancing, achieved using a collinear arrangement of three or more Mecanum wheels. The CMD has a significantly thinner ground footprint than existing omnidirectional locomotion methods, which does not need to be enlarged with increasing robot height as to avoid toppling during acceleration or external disturbance. This combination of omnidirectional manoeuvrability and a thin ground footprint allows for the creation of tall robots that are able to navigate through much narrower gaps between obstacles than existing omnidirectional locomotion methods. This allows for greater manoeuvrability in confined and cluttered environments, such as that encountered in the personal service and automated warehousing robotics sectors. This article derives the kinematics and dynamics models of the CMD, analyses controllability and accessibility, and determines the degree to which a CMD can be linearised by feedback. A partial feedback linearisation is then performed, and three practically useful nonlinear controllers are derived using a backstepping design approach, all with convergence and stability guarantees for the fully-coupled nonlinear model. These are demonstrated both in simulation and on a real-world CMD experimental prototype

Adaptive control method to manage SOC for energy storage in DC electric railways

Incorporating energy storage systems (ESSs) into electric railways has been shown to be advantageous for energy saving and power quality enhancement. For DC railways, the connection method of the ESS to the track may impose restrictions on charging and discharging the ESS to control the state of charge (SOC). Without management of the SOC, the ESS is shown in this study to reach minimum or maximum limits, reducing its effectiveness due to unavailability. Whilst it is possible to oversize the capacity of ESS, this incurs increased costs and requires more physical space. The main objective of this study is to propose and validate a control algorithm that prevents the ESS from reaching the maximum or minimum SOC limits whilst maintaining the benefits of the system. The main concept of the proposed control method is to dynamically update the voltage and current setpoints of the ESS to manage its SOC. The control algorithm is implemented in the MATLAB software and the simulation results are validated against experimental results, using a track emulator and supercapacitor. The findings demonstrate that, with appropriate dynamic charge/discharge control, the SOC levels can be adequately managed and no external load or source is required